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Crystal Structure of Human Drug Metabolizing Cytochrome P450 2C8
By Amit Shavit, 5/21/09

Protein
CYP2C8 is one of the principal hepatic drug-metabolizing enzymes that oxidizes therapeutic drugs such as taxol and cerivastatin and endobiotics such as retinoic acid and arachidonic acid. This protein has relatively large active site volume [go to Structure section and choose the green link to portray the active sites]. CYP2C8 crystallized as a symmetric dimer and is observed in solution. Furthermore, mass spectrometry confirmed the association of palmitic acid with the enzyme. This novel finding identifies a peripheral binding site in P450s that may contribute to drug-drug interactions in P450 metabolism. Perhaps an implement of Kerpolla's ingenious BiFC could provide a better understanding and monitoring of these drug-drug interactions.

Structure
This protein is a dimer. The two subunits of the dimer are visually distinguishable by their different color schemes. Moreover this protein is mostly composed of Alpha Helices, as shown in blue. While it's initially hard to tell, there are several Beta Sheets, as shown in purple. Furthermore, as most proteins contain a hydrophobic core, this protein indeed contains many Hydrophobic interactions, as shown in red, and relatively fewer Polar bonds , as shown in dark green. Lastly, the protein's Active Sites are shown in brown.

Reference
Schoch GA, Yano JK, Wester MR, Griffin KJ, Stout CD, Johnson EF Structure of human microsomal cytochrome P450 2C8. Evidence for a peripheral fatty acid binding site. J Biol Chem. 2004 Mar 5;279(10):9497-503. Epub 2003 Dec 15. PMID:14676196